Over the years, roles of microRNAs (miRNAs) in development of human diseases has been broadly investigated, while the role of dexmedetomidine (DEX) regulating miR-381-5p in myocardial ischemia-reperfusion injury (MIRI) remains largely unknown. Thus, we aimed to identify the effect of DEX on MIRI via mediating miR-381-5p.
The MIRI mice models were established by the ligation of the left anterior descending (LAD) artery and treated with miR-381-5p agomir, silenced chitinase-3-like 1 protein (CHI3L1) and DEX. The cardiac function, serum inflammatory factors, pathological changes and cardiomyocyte apoptosis of the mice' myocardial tissues were measured. The targeting relationship between miR-381-5p and CHI3L1 was predicted.
MiR-381-5p expression was decreased while CHI3L1 expression was increased in myocardial tissues of MIRI mice. DEX preconditioning could improve cardiac function and attenuate the pathological changes, cardiomyocyte apoptosis in myocardial tissues and inflammatory response in serum of MIRI mice. MiR-381-5p agomir improved the protective impact of DEX on myocardial injury in MIRI mice. Moreover, there existed a target relation between miR-381-5p and CHI3L1.
Our study demonstrated that upregulated miR-381-5p strengthens the effect of DEX preconditioning to protect against MIRI in mouse models by inhibiting CHI3L1.
Our study demonstrated that upregulated miR-381-5p strengthens the effect of DEX preconditioning to protect against MIRI in mouse models by inhibiting CHI3L1.Chronic obstructive pulmonary disease (COPD) is a disease associated with accelerated aging that threatens the lives of people worldwide and imposes heavy social and economic burdens. https://www.selleckchem.com/products/Bleomycin-sulfate.html Cellular senescence is commonly observed in COPD and contributes to aging-related diseases.
To identify the possible molecular pathways modulating cellular senescence in COPD.
MiR-494-3p expression levels in COPD tissues, small airway epithelial cells (SAECs) and BEAS-2B cells were detected by qRT-PCR. After transfection with miR-494-3p mimic or inhibitor in COPD SAECs, miR-494-3p modulation of senescence markers and senescence-associated secretory phenotype (SASP) proteins was detected. A luciferase assay was employed to verify the direct binding of SIRT3 and miR-494-3p. VX745 and c-myc siRNA were used to investigate the regulation of p38MAPK and c-myc by miR-494-3p.
As a result of oxidative stress, MiR-494-3p was increased via the p38MAPK-c-myc signaling pathway in the lung tissues and cells of patients with COPD, and the increase in miR-494-3p was accompanied by increases in senescence markers (p27, p21 and p16) and SASP proteins (IL-1β, TNF-α, MMP2 and MMP9). MiR-494-3p was directly bound to SIRT3 in SAECs and was involved in cellular senescence. The upregulation of miR-494-3p decreased SIRT3 expression while increasing p27 expression in SAECs. Inhibition of miR-494-3p in SAECs from COPD patients reduced cell cycle arrest and the expression of SASP proteins (IL-1β, TNF-α, MMP2 and MMP9).
MiR-494-3p expression can be induced by oxidative stress via the p38MAPK-c-myc signaling pathway, and miR-494-3p can directly bind to SIRT3 to reduce its expression, leading to increased cellular senescence and thereby contributing to COPD progression.
MiR-494-3p expression can be induced by oxidative stress via the p38MAPK-c-myc signaling pathway, and miR-494-3p can directly bind to SIRT3 to reduce its expression, leading to increased cellular senescence and thereby contributing to COPD progression.Although mechanical ventilation (MV) is indispensable to life-support therapy in critically ill patients, it may promote or aggravatelunginjury known asventilator-inducedlunginjury(VILI). 6-Gingerol is the principal ingredient of ginger with potential anti-inflammatory and antioxidant properties in various diseases. Nevertheless, the role and mechanism of 6-gingerol in the process of VILI has not been explicitly investigated. In the study, we found that pre-treatment with 6-gingerol significantly improved the histological changes and pulmonary oedema, inhibited neutrophil accumulation and the release of early pro-inflammatory cytokines and MPO, and reduced oxidative stress reactions after high MV. Moreover, 6-gingerol treatment also increased PPARγ expression and decreased NF-κB activation in rats subjected to high MV. Furthermore, GW9662, a specific PPARγ inhibitor, was demonstrated to activatethe NF-κB pathway and cancele the protective role of 6-gingerol in VILI. This indicates that 6-gingerol exerted anti-inflammatory and antioxidative stress effects in VILI by activating PPARγ and inhibiting the NF-κBsignalling pathway.Childhood mortality due to asthma remains problematic; however, asthma-related mortality in Korean children has not been previously described. This study aimed to estimate asthma mortality and morbidity and determine to what extent asthma contributes to childhood mortality in Korea.
Data from 9 to 12 million children (aged&lt;18 years) per year recorded for each year between 2002 and 2015 were retrieved from the Korea National Health Insurance claims database. Patients with asthma during the year preceding death were investigated. Causes of death were analysed using data obtained from the Korean Statistical Information Service database. Cause-specific mortality was examined, and the mortality rate of children with asthma was compared to that of the general paediatric population with respect to the cause of death and age. Hospital use by patients with asthma, including intensive care unit admission and hospitalisation, was analysed.
Asthma mortality decreased from 0.09 per 100,000 children in 2003 to 0.02 per 100,000 children in 2014, with an average mortality of 0.06 per 100,000 children. Mortality due to respiratory diseases was four times more common in patients with asthma than in the general population of children aged &gt;5 years, despite decreases in asthma-related mortality. Asthma-related hospitalisations and intensive care interventions tended to decrease throughout the study period.
Asthma mortality declined in children between 2003 and 2015 in Korea. Children with asthma are at a higher risk of death from respiratory diseases than the general population.
Asthma mortality declined in children between 2003 and 2015 in Korea. Children with asthma are at a higher risk of death from respiratory diseases than the general population.